With new book, LSI professor wants to help researchers navigate genetic models for studying Down syndrome
Developmental biologist Bing Ye, Ph.D., has studied the genetics of Down syndrome for more than a decade, using multiple model systems to investigate how the genes found on human chromosome 21 contribute to the myriad symptoms found in patients with this condition.
Building in part on his own experience, Ye has now edited and co-authored a new book, Genetic Models of Down Syndrome, that he hopes will help current researchers and newcomers to the field capitalize on the variety of tools and systems available to continue advancing new understandings and potential therapies for Down syndrome. He recently answered questions about the motivation behind the book and what he hopes this resource will bring to the field. (Responses have been edited for length.)
What you motivated you to edit, compile, create this book? How did it get started?
I recognized that we were lacking this type of book in the field of Down Syndrome research — one resource that covers all the different genetic models. I use Drosophila (fruit flies), to study mechanisms of Down Syndrome. There isn't a book, or even a review article, on how to use Drosophila to study Down syndrome and the strengths and limitations. Researchers who use zebrafish or C. elegans have a similar situation.
So, I knew we needed this kind of resource, but I never thought that I would write or edit a book. But a couple of years ago, I participated in a symposium about the genetic models of Down syndrome. Afterward, an editor from Springer Nature contacted me, asking if I would be interested in writing a book on this. I discussed it with the other symposium presenters, we discussed the need for this and how it could be done. After that, I got to work on it.
Serving as the editor, you were responsible for organizing the chapters and authors. How did you pick who was going to write each chapter?
Based on their publications, their expertise in the field. Every senior author of each chapter is a leader in that area. So, for example, for the C. elegans chapter, the authors had to be experts in C. elegans research who were also major researchers in the Down syndrome field. The symposium presenters became some of the chapter authors or helped invite other authors.
Within this Down syndrome book, there is a lot of very useful information for people who want to learn about the advantages and limitations of different model organisms, which can then be applied to a variety of research fields.
So, what is the value of having all of these different model systems? What do the different models enable that would necessitate using multiple species to study this disorder?
Like any other medical condition that scientists study, directly studying humans will be very limited. Even for human models, it's cell- or tissue-based models. One of the main ways we can study the mechanisms of the disorder, such as how the genes function in an organism, is by using these various animal models — C. elegans, Drosophila, zebrafish, rodents and others. And they each have their own unique advantages and weaknesses.
For example, many cells and tissues in flies resemble their counterparts in mammals. So, you could use these cells and tissues as a model, and then change the genes to see how the Down syndrome chromosome 21 genes affect their development. C. elegans are great for performing larger-scale genetic screens to match specific genes with changes in physiological characteristics. But neither of these are vertebrates. Zebrafish offer a vertebrate model that still has very powerful genetic tools. Rodents are mammals, so they offer more insight into how the disorder affects mammals; but because of their lifespan and complexity, they cannot be used for the types of genetic studies we can do in flies, C. elegans, or zebrafish. There are also aspects that are unique to humans, so studying human cell culture lets us investigate those aspects, but not within the context of a whole organ or organism.
Each system lets you do things that other systems cannot do, and they work together as a discovery pathway — from less complex genetic models all the way through human. Studies in flies and C. elegans have offered therapeutic ideas that can then be tested in vertebrates, for example, to see whether a treatment could be developed for clinical trials.
In the foreword, you outline the target audiences for the book. What do you hope these audiences will gain from this book?
Since we have now put all of these different models together and explained them in this one resource, I hope it lowers the barrier for new people to enter the research field. It provides a starting point so they can know the status of the field, the models available, and the strengths and weaknesses of each. And I think that last aspect is an important feature of the book. All of the authors agreed that we should not just advocate for our own models. We do that to some extent, of course, but we also emphasize the limitations of each model so that the researchers can know when to use it and when not to use it. I think that's equally important.
What else would you want potential audiences to know about the book?
I think that this book can also be used by researchers who don't work on Down syndrome but are interested in using genetic models to study various diseases or even basic science. In each chapter, we start by explaining what the genetic system is and the major techniques we use with that system, before we get into the Down syndrome research. So, within this Down syndrome book, there is a lot of very useful information for people who want to learn about the advantages and limitations of different model organisms, which can then be applied to a variety of research fields.